Author Information

The environmental controls that have been developed over the last quarter century have, for the most part, been designed to reduce respiratory disease and cancer. In contrast, public health measures designed to reduce heart disease have concentrated on individual risk factors (1). Over the last decade, however, there has been growing epidemiological evidence that elevated levels of air pollution, particularly increased levels of fine particulates (smaller than 10 μm in diameter, PM10or 2.5 μm, PM2.5), are associated with increased hospitalization (2)and mortality from cardiovascular disease (3–5).

The study by Suwa et al. (6)in this issue of the Journalprovides important experimental evidence to support the conclusion that these epidemiological results are reflecting real effects of particulate pollution directly on the cardiovascular system. The investigators present convincing experimental evidence that particulate air pollution induces progression of atherosclerosis. They exposed rabbits to small particles (most <3 μm) collected from outdoor air in Ottawa, Canada by intrapharyngeal installation twice a week for four weeks, then measured responses in the lung, bone marrow, coronary arteries and aorta. The delivered dose at the level of the alveolar surface, estimated to be 23.2 ng/cm2, was less than the estimated human exposure of 35.1 ng/cm2based on average pollution levels in six U.S. cities (3). Compared to a control group, the rabbits exposed to the particles from the air pollution experienced a systemic inflammatory response that included bone marrow stimulation and progression of atherosclerotic lesions in the coronary arteries and aorta. The extent of the atherosclerotic effects correlated with the extent of particulates phagocytosed by alveolar macrophages in the lung. The rabbits exposed to particulates had more advanced phenotypes of coronary lesions and increased plaque size. There was histological evidence of more extensive atherosclerosis in the aorta, an increase in the volume fraction of the lesions made up of lipids, and increased cell turnover. Plaques with these characteristics are more likely to rupture and trigger a coronary event than collagenous plaques (7,8).

The results reported by Suwa et al. (6)are consistent with human studies that found elevated levels of C-reactive protein, a marker of systemic inflammation, in people during times of increased particulate air pollution (9,10). During increased levels of particulate air pollution, individuals experience elevated levels of plasma viscosity (11)and other changes in blood chemistry, suggesting that the adhesive properties of red blood cells are increased (10). These changes would predict an increased risk of a coronary event during periods of heightened air pollution.

Further support that these changes are due to the effects of air pollution comes from studies of the effects of secondhand tobacco smoke, which is, after all, indoor air pollution. Even short-term exposure to secondhand smoke increases platelet activation (12,13). Secondhand smoke also promotes atherosclerosis (14–16). This effect does not depend on the nicotine in the smoke (17), further implicating general products of combustion of organic matter, similar to those products observed in outdoor air pollution. The fact that exposure to the secondhand smoke of just one cigarette a day accelerated the atherosclerotic process (15)also suggests that low doses of air pollutants can have important effects on the coronary circulation. Other organic pollutants, 7,12-dimethylbenz(a)anthracene (18)and 1,3-butadiene (19), are atherogenic in experimental animals exposed via inhalation.

Although the precise mechanisms by which exposure to particulates affects the autonomic nervous system are unclear, there is strong and consistent evidence that increases in the level of particulate air pollution are associated with reduced heart rate variability (20,21)and increases in heart rate (22)and blood pressure (23,24). Decreased heart rate variability predicts a higher risk of cardiac death or arrhythmic events after acute myocardial infarction (MI), presumably reflecting the adverse effects of increased sympathetic tone (25,26). In addition to epidemiological evidence that increased air pollution produces these effects, similar changes were observed in a quasi-experimental study of boilermakers, which found that significant reductions in heart rate variability were associated with just a few hours of occupational exposure to increased particulate levels (27). Likewise, an experimental study of the effects of secondhand smoke on heart rate variability showed an average 12% reduction in heart rate variability after just 2 h of exposure in an airport smoking lounge (28). A study of 100 patients with implanted cardioverter-defibrillators (ICDs) observed a higher rate of discharges within two days of periods of elevated air pollution (NO, CO, fine carbon, and fine particulates), indicating an increased incidence of potentially life-threatening arrythmias (29).

Secondhand smoke exposures produce rapid (in 30 min in human studies) deterioration in endothelial function in experimental animals (30)and humans (31–33). Secondhand smoke also increases infarct size in experimental animals (16), an effect that can be partially blocked by administering L-arginine, which helps restore endothelial function (34). To date, there have not been studies of the effects of air pollution on endothelial function, but it is likely that some of the effects observed in the epidemiological studies are due to the influence of air pollution on endothelial function. This is a question worthy of future research.

Finally, increases in air pollution are associated with increased risk of MI (29,35). A study in Boston reported that these effects occur quickly; the odds of an MI were significantly increased (odds ratio [OR] = 1.48, 95% confidence interval [CI], 1.09–2.02) with an incr]ease in airborne particulate concentrations of 25 μg/m3during the 2-h period before the onset of the MI and an OR of 1.69 (95% CI, 1.13–2.34) for an increase of 20 μg/m3in the 24 h before event onset (29).

All these effects indicate that air pollution has an impact on heart disease. Some of these effects may occur over time, as with acceleration of the progression of atherosclerosis, or very quickly, as with an increase in the risk of an arrhythmia or MI by acute inflammatory responses, altering platelet function, or, perhaps, endothelial function. These effects may be independent of, or synergistic with, alterations in autonomic tone as reflected in increases in heart rate and reductions in heart rate variability.

In any event, it is clear that these risks are real and substantial. Indeed, of the estimated 53,000 deaths due to secondhand smoke, 37,000 are attributed to cardiovascular disease compared with only 3,000 attributed to lung cancer (12). (Other estimates put the cardiovascular death estimate as high as 62,000 [36].) If outdoor air pollution exhibits a similar pattern of risks, the toll due to heart disease could be much larger—and more immediate—than the burden of cancer and lung disease that has been used to develop current air pollution standards.

It is time for organizations concerned with heart health, including the American College of Cardiology and the American Heart Association, as well as traditional environmental organizations and environmental regulators, to consider seriously the cardiovascular effects of air pollution when developing and implementing standards to clear the air and protect public health.

Footnotes

☆ Preparation of this editorial was supported by the Richard and Rhoda Goldman Fund.

↵* Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.

Toolbox

Thank you for your interest in spreading the word about JACC: Journal of the American College of CardiologyNOTE: We request your email address only as a reference for the recipient. We do not save email addresses.

Your Email *

Your Name *

Send To *

Enter multiple addresses on separate lines or separate them with commas.